1. Case Report- ES Andrew Rosenzweig, MD 9.21.07

2. Background 70 year old Caucasian female Generalized anxiety disorder Depression Progressive memory loss Hyperlipidemia Osteopenia

3. Background Lives alone in Philadelphia Independent in BADLs and IADLs 43 pack year tobacco history, quit 1990 One “watered-down” martini/day Up to date on routine health care maintenance Family history- mother died from lung cancer

4. Background October 2003- voluntarily participated in National Lung Screening Trial Compare non-contrast CT vs CXR- 1 study annually for 3 years in patients aged 55-74 who smoked for at least 30 years and had quit within the prior 15 years

5. CT 10/24/03 3 x 3 mm diffusely calcified granuloma within the left upper lobe 2 x 2 mm ground glass density smooth round nodule within the anterolateral left upper lobe, which is likely benign in etiology. 8 x 6 mm soft tissue density smooth curvilinear nodule within the anterior left lower lobe adjacent to the major fissure, which is indeterminate in etiology. 2 x 2 mm soft tissue density smooth round nodule within the anterior right upper lobe, which is likely benign in etiology. 3 x 3 mm soft tissue density smooth round nodule within the anterolateral right upper lobe, which is likely benign in etiology. There is mild biapical scarring. There is mild centrilobular emphysema. Thin-section chest CT 3 months from screening exam.

6. CT 12/2/04 There is a stable 3 mm calcified granuloma within the left upper lobe There is a stable 2 mm calcified granuloma within the left upper lobe. There is a stable 8 x 6 mm soft tissue density smooth ovoid nodule within the anterior left lower lobe adjacent to the major fissure, which is probably benign in etiology. There is a new 4 x 2 mm faintly visualized soft tissue density smooth ovoid nodule within the anterior left lower lobe, which is indeterminate in etiology. There is a stable 3 x 2 mm soft tissue density smooth ovoid nodule within the anterior right upper lobe, which is likely benign in etiology. There is a stable 3 x 3 mm soft tissue density smooth round nodule within the anterolateral right upper lobe, which is likely benign in etiology. There is a new 3 x 3 mm ground glass density smooth round nodule within the posterolateral right lower lobe, which is indeterminate but probably benign in etiology.

7. CT 10/14/05 There is a stable 2 x 2 mm soft tissue density smooth round nodule within the posterior left upper lobe, which is likely benign in etiology. There is a stable 8 x 6 mm soft tissue density smooth ovoid nodule within the anterior left lower lobe adjacent to the major fissure, which is likely benign in etiology. The previously noted 4 mm soft tissue density nodule within the anterior left lower lobe is no longer visualized, in keeping with an inflammatory etiology. There is a stable 2 x 2 mm soft tissue density smooth round nodule within the anterior right upper lobe, which is likely benign in etiology. There is a stable 3 x 3 mm soft tissue density smooth round nodule within the anterolateral right upper lobe, which is likely benign in etiology. There is a stable 3 x 3 mm ground glass density smooth round nodule within the posterolateral right lower lobe, which is probably benign in etiology. There is a new 4 x 4 mm ground glass density smooth round nodule within the posterior right lower lobe, which is indeterminate in etiology. There is a new 3 x 3 mm soft tissue density smooth round nodule within the inferior right middle lobe, which is indeterminate in etiology.

8. CT 8/9/07 Comments: There is very minimal centrilobular emphysema involving the apical portions of the lungs. There is also a sense of very fine ground glass centrilobular nodules seen throughout the lungs bilaterally. This pattern is most likely a manifestation of respiratory bronchiolitis interstitial lung disease. Is this patient a smoker? Several calcified granulomas are noted in the apical portions of the lungs. Of the small pulmonary nodules reported previously, there is only one nodule that persists. This is seen adjacent to the major fissure on image 33 and now measures approximately 4 x 3 mm. This is stable from films going back to October 24, 2003 and is consistent with a small benign nodule. No further follow-up is necessary. Impression: 1. Minimal centrilobular emphysema. 2. Possible respiratory bronchiolitis interstitial lung disease. 3. Stable small benign left lower lobe nodule, no further follow-up necessary.

9. Multiple Pulmonary Nodules Most commonly- Metastatic solid organ malignancies- 80% Lesions are variable in size and location- usually round with sharply demarcated borders Non-Hodgkin's lymphoma Kaposi's sarcoma Infection- multiple abscesses in bacteremic patients, fungi Septic emboli Wegener's granulomatosis Pulmonary arteriovenous malformations Pneumoconiosis and silicosis Helical CT is the method of choice for detection

10. Solitary Pulmonary Nodule (SPN) Lesion that is both within and surrounded by pulmonary parenchyma Initial evaluation used to determine the probability that the nodule is malignant The probability of a SPN being malignant rises with increasing patient age: - 3% in patients between ages 35 and 39 - 15% between ages 40 and 49 - 43% between ages 50 and 59 - 50% or higher at age 60 or above Risk factors- cigarette smoking, asbestos exposure, family history, prior malignancy

11. Causes of SPN Malignant- Bronchogenic carcinoma, Adenocarcinoma, Squamous cell carcinoma, Large cell carcinoma, Small cell carcinoma Metastatic lesions- Breast, Head and neck, Melanoma, Colon, Kidney, Sarcoma, Germ cell tumor, Others Pulmonary carcinoid Infectious granuloma- Histoplasmosis, Coccidioidomycosis, Tuberculosis, Atypical mycobacteria, Cryptococcosis, Blastomycosis Other infections- Bacterial abscess, Dirofilaria immitis, Echinococcus cyst, Ascariasis, Pneumocystis carinii, Aspergilloma Benign neoplasms- Hamartoma, Lipoma, Fibroma, Vascular- Arteriovenous malformation, Pulmonary varix Developmental- Bronchogenic cyst Inflammatory- Wegener's granulomatosis, Rheumatoid nodule Other- Amyloidoma, Rounded atelectasis, Intrapulmonary lymph nodes, Hematoma, Pulmonary infarct, Pseudotumor (loculated fluid), Mucoid impaction

12. Radiographic features Size — Larger lesions are more likely to be malignant than smaller lesions- likelihood of malignancy was 0.2 percent for nodules smaller than 3 mm up to 50 percent for nodules larger than 20 mm Border — Malignant lesions tend to have more irregular and spiculated borders, whereas benign lesions often have a relatively smooth and discrete border. Density- Increased density of a SPN argues against malignancy Growth- Lesions that are malignant tend to have a volume doubling time between 20 and 400 days Therefore, a SPN whose size has increased very rapidly or has remained stable for a prolonged duration is likely benign.

14. Serial CT scans Nodule Size (mm) Low-risk patientHigh-risk patient <4No follow-up neededFollow-up CT at 12 months; if unchanged, no further follow-up >4-6Follow-up CT at 12 months; if unchanged, no further follow-up Initial follow-up CT at 6-12 months then at 18-24 months if no change >6-8Initial follow-up CT at 6-12 months then at 18-24 months if no change Initial follow-up CT at 3-6 months then at 9-12 and 24 months if no change >8Follow-up CT at around 3, 9, and 24 months, dynamic contrast- enhanced CT, PET, and/or biopsy Same as for low-risk patient

15. American College of Chest Physicians 2nd ed. of clinical practice guidelines Tissue diagnosis is recommended, unless specifically contraindicated, for an SPN that shows clear evidence of growth on imaging tests (1C). An SPN that is stable on imaging tests for at least 2 years does not require additional diagnostic evaluation, except that patients with pure ground-glass opacities on CT should have a longer duration of annual follow-up (2C). An SPN that is calcified in a clearly benign pattern does not require additional diagnostic evaluation (1C). Patients with an indeterminate SPN that measures at least 8 to 10 mm who undergo observation need serial CT scans repeated at least at 3, 4, 12, and 24 months.

16. American College of Chest Physicians 2nd ed. of clinical practice guidelines Patients with an indeterminate SPN that measures at least 8 to 10 mm and who are candidates for curative treatments need transthoracic needle biopsy, especially for peripheral nodules, or bronchoscopy For the patient with malignant SPN who is not a surgical candidate and who prefers treatment, referral for external beam radiation or to a clinical trial of an experimental treatment such as stereotactic radiosurgery or radiofrequency ablation is recommended.

17. Ground Glass Opacities Pulmonary edema Hemorrhage Interstitial pneumonias (UIP, DIP, LIP, and acute) Hypersensitivity pneumonia Atypical infectious pneumonias such as Pneumocystis carinii, mycoplasma, or CMV pneumonia Cryptogenic organizing pneumonia. Atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and adenocarcinoma

18. FDG-PET 18-flourodeoxyglucose positron emission tomography Malignancies are metabolically active and take up FDG avidly 95% sensitive, 78% specific Poor positive predictive value- infectious, inflammatory, or granulomatous nodules may be read as malignant

19. Nodule Sampling Fiberoptic bronchoscopy- large, central nodules Washing, brushing or biopsy Percutaneous needle aspiration of a SPN can be performed through the chest wall using either fluoroscopy or CT Obtains material for cytology but not a core biopsy Transthoracic needle biopsy to obtain a core of tissue with a cutting needle

20. Surgical Resection Thoracotomy Video assisted thoracic surgery (VATS)